Real-time tracking of virus evolution

Trevor Bedford (@trvrb)
26 Mar 2018
Annual International Symposium
Institute for Systems Biology

Spread of plague in 14th century

Spread of swine flu in 2009

Sequencing to reconstruct pathogen spread

Epidemic process

Sample some individuals

Sequence and determine phylogeny

Sequence and determine phylogeny

Localized Middle Eastern MERS-CoV phylogeny

Regional West African Ebola phylogeny

Global influenza phylogeny

Phylogenetic tracking has the capacity to revolutionize epidemiology

Outline

• Ebola spread in West Africa
• Zika spread in the Americas
• "Real-time" analyses

Ebola

Virus genomes reveal factors that spread and sustained the Ebola epidemic

with Gytis Dudas, Andrew Rambaut, Luiz Carvalho, Marc Suchard, Philippe Lemey,
and many others

Sequencing of 1610 Ebola virus genomes collected during the 2013-2016 West African epidemic

Phylogenetic reconstruction of evolution and spread

Tracking migration events

Factors influencing migration rates

Effect of borders on migration rates

Spatial structure at the country level

Substantial mixing at the regional level

Regional outbreaks due to multiple introductions

Zika

Zika's arrival and spread in the Americas

Establishment and cryptic transmission of Zika virus in Brazil and the Americas

with Nuno Faria, Nick Loman, Oli Pybus, Luiz Alcantara, Ester Sabino, Josh Quick,
Alli Black, Ingra Morales, Julien Thézé, Marcio Nunes, Jacqueline de Jesus,
Marta Giovanetti, Moritz Kraemer, Sarah Hill and many others

Road trip through northeast Brazil to collect samples and sequence

Case reports and diagnostics suggest initiation in northeast Brazil

Phylogeny infers an origin in northeast Brazil

Genomic epidemiology reveals multiple introductions of Zika virus into the United States

with Nathan Grubaugh, Kristian Andersen, Jason Ladner, Gustavo Palacios, Sharon Isern, Oli Pybus, Moritz Kraemer, Gytis Dudas, Amanda Tan, Karthik Gangavarapu, Michael Wiley, Stephen White, Julien Thézé, Scott Michael, Leah Gillis, Pardis Sabeti, and many others

Outbreak of locally-acquired infections focused in Miami-Dade county

Phylogeny shows introductions from the Caribbean and a surprising degree of clustering

Flow of infected travelers greatest from Caribbean

Clustering suggests fewer, longer transmission chains and higher R₀

Genomic epidemiology of Zika in the US Virgin Islands

with Alli Black, Barney Potter, Gytis Dudas, Esther Ellis, Brett Ellis,
Kristian Andersen, Nathan Grubaugh, Leora Feldstein, and others
(and special thanks to Adam Geballe)

Preliminary analysis of 31 genomes shows multiple introductions to USVI

Actionable inferences

Genomic analyses were mostly done in a retrospective manner

Key challenges to making genomic epidemiology actionable

• Timely analysis and sharing of results critical
• Dissemination must be scalable
• Integrate many data sources
• Results must be easily interpretable and queryable

nextstrain

Project to conduct real-time molecular epidemiology and evolutionary analysis of emerging epidemics

with Richard Neher, James Hadfield, Colin Megill,
Sidney Bell, John Huddleston, Barney Potter,
and Charlton Callender

Nextstrain architecture

All code open source at github.com/nextstrain

Rapid on-the-ground sequencing by Ian Goodfellow, Matt Cotten and colleagues

Desired analytics are pathogen specific and tied to response measures

Build out pipelines for different pathogens, improve databasing and lower bioinformatics bar

Acknowledgements

Bedford Lab: Alli Black, Sidney Bell, Gytis Dudas, John Huddleston,
Barney Potter, James Hadfield, Louise Moncla

Ebola: Gytis Dudas, Andrew Rambaut, Luiz Carvalho, Philippe Lemey, Marc Suchard, Andrew Tatem

Zika: Nick Loman, Nuno Faria, Oli Pybus, Josh Quick, Kristian Andersen, Nathan Grubaugh, Jason Ladner, Gustavo Palacios, Sharon Isern, Gytis Dudas, Alli Black, Barney Potter, Louise Moncla, Esther Ellis

Nextstrain: Richard Neher, James Hadfield, Colin Megill, Sidney Bell, Charlton Callender, Barney Potter, John Huddleston